Total flavones of Abelmoschus manihot improve diabetic nephropathy by inhibiting the iRhom2/TACE signalling pathway activity in rats
Context: Total flavones extracted from Abelmoschus manihot L. (Malvaceae) medic (TFA) have been proven clinically effective at improving renal inflammation and glomerular injury in chronic kidney disease (CKD). Objective: This study evaluated the function of TFA as an inhibitor of iRhom2/TACE (tumou...
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doaj-5dfc6a8195f642d687506d5ce5b621972020-11-25T02:09:52ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162018-01-0156111110.1080/13880209.2017.14124671412467Total flavones of Abelmoschus manihot improve diabetic nephropathy by inhibiting the iRhom2/TACE signalling pathway activity in ratsSu Liu0Lifang Ye1Jing Tao2Chao Ge3Liji Huang4Jiangyi Yu5Jiangsu Province Hosipital of TCM, Affiliated Hospital of Nanjing University of Chinese MedicineJiangsu Province Hosipital of TCM, Affiliated Hospital of Nanjing University of Chinese MedicineJiangsu Province Hosipital of TCM, Affiliated Hospital of Nanjing University of Chinese MedicineJiangsu Province Hosipital of TCM, Affiliated Hospital of Nanjing University of Chinese MedicineJiangsu Province Hosipital of TCM, Affiliated Hospital of Nanjing University of Chinese MedicineJiangsu Province Hosipital of TCM, Affiliated Hospital of Nanjing University of Chinese MedicineContext: Total flavones extracted from Abelmoschus manihot L. (Malvaceae) medic (TFA) have been proven clinically effective at improving renal inflammation and glomerular injury in chronic kidney disease (CKD). Objective: This study evaluated the function of TFA as an inhibitor of iRhom2/TACE (tumour necrosis factor-α converting enzyme) signalling and investigated its anti-DN (diabetic nephropathy) effects in a DN rat model. Materials and methods: In vitro, cells were treated with 200 μg/mL advanced glycation end products (AGEs), and then co-cultured with 20 μg/mL TFA for 24 h. Real time PCR, western blotting and co-immunoprecipitation assays were performed. In vivo, DN was induced in 8 week old male Sprague-Dawley rats via unilateral nephrectomy and intraperitoneal injection of streptozotocin, then TFA were administered to rats by gavage for 12 weeks at three different doses (300, 135 and 75 mg/kg/d). 4-Phenylbutanoic acid (2.5 mg/kg/d) was used as a positive control. Results: IC50 of TFA is 35.6 μM in HK2 and 39.6 μM in HRMC. TFA treatment (20 μM) inhibited the activation of iRhom2/TACE signalling in cultured cells induced by AGEs. LD50>26 g/kg and ED50=67 mg/kg of TFA in rat by gavage, TFA dose-dependently downregulated the expression of proinflammatory cytokines and exerted anti-inflammatory effects significantly though inhibiting the activation of iRhom2/TACE signalling. Discussion and conclusions: Our results show that TFA could dose-dependently ameliorate renal inflammation by inhibiting the activation of iRhom2/TACE signalling and attenuating ER stress. These results suggest that TFA has potential therapeutic value for the treatment of DN in humans.http://dx.doi.org/10.1080/13880209.2017.1412467tfaendoplasmic reticulum stressrenal injuryages |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Su Liu Lifang Ye Jing Tao Chao Ge Liji Huang Jiangyi Yu |
spellingShingle |
Su Liu Lifang Ye Jing Tao Chao Ge Liji Huang Jiangyi Yu Total flavones of Abelmoschus manihot improve diabetic nephropathy by inhibiting the iRhom2/TACE signalling pathway activity in rats Pharmaceutical Biology tfa endoplasmic reticulum stress renal injury ages |
author_facet |
Su Liu Lifang Ye Jing Tao Chao Ge Liji Huang Jiangyi Yu |
author_sort |
Su Liu |
title |
Total flavones of Abelmoschus manihot improve diabetic nephropathy by inhibiting the iRhom2/TACE signalling pathway activity in rats |
title_short |
Total flavones of Abelmoschus manihot improve diabetic nephropathy by inhibiting the iRhom2/TACE signalling pathway activity in rats |
title_full |
Total flavones of Abelmoschus manihot improve diabetic nephropathy by inhibiting the iRhom2/TACE signalling pathway activity in rats |
title_fullStr |
Total flavones of Abelmoschus manihot improve diabetic nephropathy by inhibiting the iRhom2/TACE signalling pathway activity in rats |
title_full_unstemmed |
Total flavones of Abelmoschus manihot improve diabetic nephropathy by inhibiting the iRhom2/TACE signalling pathway activity in rats |
title_sort |
total flavones of abelmoschus manihot improve diabetic nephropathy by inhibiting the irhom2/tace signalling pathway activity in rats |
publisher |
Taylor & Francis Group |
series |
Pharmaceutical Biology |
issn |
1388-0209 1744-5116 |
publishDate |
2018-01-01 |
description |
Context: Total flavones extracted from Abelmoschus manihot L. (Malvaceae) medic (TFA) have been proven clinically effective at improving renal inflammation and glomerular injury in chronic kidney disease (CKD). Objective: This study evaluated the function of TFA as an inhibitor of iRhom2/TACE (tumour necrosis factor-α converting enzyme) signalling and investigated its anti-DN (diabetic nephropathy) effects in a DN rat model. Materials and methods: In vitro, cells were treated with 200 μg/mL advanced glycation end products (AGEs), and then co-cultured with 20 μg/mL TFA for 24 h. Real time PCR, western blotting and co-immunoprecipitation assays were performed. In vivo, DN was induced in 8 week old male Sprague-Dawley rats via unilateral nephrectomy and intraperitoneal injection of streptozotocin, then TFA were administered to rats by gavage for 12 weeks at three different doses (300, 135 and 75 mg/kg/d). 4-Phenylbutanoic acid (2.5 mg/kg/d) was used as a positive control. Results: IC50 of TFA is 35.6 μM in HK2 and 39.6 μM in HRMC. TFA treatment (20 μM) inhibited the activation of iRhom2/TACE signalling in cultured cells induced by AGEs. LD50>26 g/kg and ED50=67 mg/kg of TFA in rat by gavage, TFA dose-dependently downregulated the expression of proinflammatory cytokines and exerted anti-inflammatory effects significantly though inhibiting the activation of iRhom2/TACE signalling. Discussion and conclusions: Our results show that TFA could dose-dependently ameliorate renal inflammation by inhibiting the activation of iRhom2/TACE signalling and attenuating ER stress. These results suggest that TFA has potential therapeutic value for the treatment of DN in humans. |
topic |
tfa endoplasmic reticulum stress renal injury ages |
url |
http://dx.doi.org/10.1080/13880209.2017.1412467 |
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